OBJECTIVETo assess protein and mRNA expression levels of heparanase and basic fibroblast growth factor (bFGF) genes in human non-small cell lung cancer (NSCLC) and their roles in tumor invasion, metastasis and prognosis.

METHODSA total of 115 paraffin-embedded and 45 fresh-frozen tissue specimens of NSCLC were studied by immunohistochemistry, Western Blot and in situ hybridization to evaluate the protein and mRNA expression status of heparanase and bFGF genes. The data was analyzed by SPSS statistical software.

RESULTSBoth human heparanase and bFGF were highly expressed in NSCLC cells, in contrast to none or a low expression in normal lung tissue. Expression of heparanase also showed a significantly higher than that in the normal tissue by Western blot (P = 0.041). Immunohistochemistry showed that heparanase expression was both cytoplasmic and membranous. The agreement between heparanase and bFGF was significant. A significant correlation was found between the expression of either protein and TNM stage, vascular invasion, lymphatic metastasis and microvascular density (MVD). Co-expression of the two proteins demonstrated an even higher correlation with the tumor stage and MVD. In addition, expression of bFGF correlated with tumor cell differentiation. Data of a multivariate analysis indicated that tumor cell differentiation, vascular invasion, lymphatic metastasis and expression of bFGF were identified as significant prognostic parameters.

CONCLUSIONSBoth heparanase and bFGF may play important roles in tumor angiogenesis, metastasis, and prognosis of NSCLC.

Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; enzymology ; metabolism ; pathology ; Cell Differentiation ; Female ; Fibroblast Growth Factor 2 ; metabolism ; Glucuronidase ; metabolism ; Humans ; Lung Neoplasms ; enzymology ; metabolism ; pathology ; Lymphatic Metastasis ; Male ; Microcirculation ; pathology ; Middle Aged ; Neoplasm Staging ; Neovascularization, Pathologic ; Prognosis ; Survival Rate

BACKGROUNDTo study the relationship between human heparanase expression and biological factors regarding invasion, metastasis and prognosis of human non-small cell lung cancer (NSCLC).

METHODSThe expression of heparanase was assessed in 122 paraffin-embedded specimens and 38 freshly-taken tissues by immunohistochemical staining and Western blot. The relationship between heparanase expression and the clinicopathological factors was analyzed by Chi square test, multivariate analysis and Kaplan-Meier method.

RESULTSIn the immunoreactive cells, staining was mainly located in cytoplasma and membrane. Human heparanase was highly expressed in lung cancer tissues (78.7%, 96/122) while negative in epithelia of normal lung tissues. The level of heparanase was remarkably higher in NSCLC than that in normal tissues ( P = 0.043 ). Expression of heparanase significantly correlated with TNM stage ( P =0.025), lymphatic metastasis ( P =0.002) and vascular invasion ( P =0.000 3). The patients with positive heparanase expression had a significantly shorter survival than those with negative heparanase expression ( P =0.000 6). In multivariate analysis, only p-TNM stage, lymphatic metastasis and vascular invasion could be considered as prognostic factors.

CONCLUSIONSHeparanase might play an important role in the development, invasion and metastasis of NSCLC. It is indicated that patients with positive heparanase expression would have a greater chance of metastasis and a poorer prognosis. However, heparanase expression is not an independent prognostic factor.